Aryl derivatives Stille cross-coupling

Chloropyridazines seem to be preferred over 3-iodopyridazincs in this type of crosscoupling reaction [50]. Maes and co-workers compared Stille reactions of 6-chloropyridazin-3-amine and 6-iodopyridazin-3-amine under identical reaction conditions. Remarkably, using the same aryl(tributyl)stannane cross-coupling on the chloropyridazine was substantially faster than the same reaction on the corresponding iodo derivative although oxidative addition on the latter is certainly easier. 

The synthesis starts with 2,4-dibromothiazole (40), a regioselective Pd(0)-catalysed cross coupling step introduces a substituent at the 2-position. Alkyl or aryl zinc halides were employed as the nucleophiles to give 41. The 4-bromothiazole derivative 41 was then converted into a carbon nucleophile either as a zinc derivative (Negishi conditions) or as a tin derivative (Stille conditions) which then underwent a second cross coupling reaction with 2,4-dibromothiazole (40) to give exclusively 2 ,4-disubstituted 2,4 -bithiazoles 42. 

Stille reaction between a tin derivative of 7-azaindole 627 and the aryl or heteroaryl halide proved to be more useful than Suzuki, Negishi, or other Pd-catalyzed cross-coupling reactions for the formation of aryl or heteroaryl-7-azaindoles 628 (Scheme 127) <2004M615>. 

One distinguishes palladium(0)- and palladium(ll)-catalysed reactions. The most common palladium(O) transformations are the Mizoroki-Heck and the cross-coupling transformations such as the Suzuki-Miyaura, the Stille and the Sonogashira reactions, which allow the arylation or alkenylation of C=C double bonds, boronic acid derivates, stan-nanes and alkynes respectively [2]. Another important palladium(O) transformation is the nucleophilic substitution of usually allylic acetates or carbonates known as the Tsuji-Trost reaction [3]. The most versatile palladium(ll)-catalysed transformation is the Wacker oxidation, which is industrially used for the synthesis of acetaldehyde from ethylene [4]. It should be noted that many of these palladium-catalysed transformations can also be performed in an enantioselective way [5]. 

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